CA2368626C - Cilostazol preparation - Google Patents

Cilostazol preparation Download PDF

Info

Publication number: CA2368626C
Authority: CA; Canada
Prior art keywords: cilostazol; preparation; sustained release; fine powder; preparation according
Prior art date: 1999-03-25
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2368626A

Other languages

English (en)

French (fr)

Other versions

CA2368626A1 (en

Inventor

Tadashi Mukai

Yuso Tomohira

Masafumi Toda

Keigo Yamada

Yoshikazu Oka

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Otsuka Pharmaceutical Co Ltd

Original Assignee

Otsuka Pharmaceutical Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-03-25

Filing date

2000-03-21

Publication date

2010-02-16

2000-03-21 Application filed by Otsuka Pharmaceutical Co Ltd filed Critical Otsuka Pharmaceutical Co Ltd

2000-10-05 Publication of CA2368626A1 publication Critical patent/CA2368626A1/en

2010-02-16 Application granted granted Critical

2010-02-16 Publication of CA2368626C publication Critical patent/CA2368626C/en

2020-03-21 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

229960004588 cilostazol Drugs 0.000 title claims abstract description 419
RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 title claims abstract description 419
238000002360 preparation method Methods 0.000 title claims abstract description 132
239000000843 powder Substances 0.000 claims abstract description 143
210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 67
239000002904 solvent Substances 0.000 claims abstract description 60
239000002270 dispersing agent Substances 0.000 claims abstract description 58
238000000034 method Methods 0.000 claims abstract description 27
230000008569 process Effects 0.000 claims abstract description 17
239000003826 tablet Substances 0.000 claims description 158
239000008187 granular material Substances 0.000 claims description 120
239000002245 particle Substances 0.000 claims description 85
239000003405 delayed action preparation Substances 0.000 claims description 68
238000013268 sustained release Methods 0.000 claims description 53
239000012730 sustained-release form Substances 0.000 claims description 53
239000002775 capsule Substances 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 42
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 41
-1 fatty acid ester Chemical class 0.000 claims description 41
235000019333 sodium laurylsulphate Nutrition 0.000 claims description 41
239000004094 surface-active agent Substances 0.000 claims description 34
239000000463 material Substances 0.000 claims description 27
239000011248 coating agent Substances 0.000 claims description 24
238000000576 coating method Methods 0.000 claims description 23
239000007939 sustained release tablet Substances 0.000 claims description 15
235000014113 dietary fatty acids Nutrition 0.000 claims description 13
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229930195729 fatty acid Natural products 0.000 claims description 13
229920003169 water-soluble polymer Polymers 0.000 claims description 10
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ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 5
229930006000 Sucrose Natural products 0.000 claims description 4
150000005215 alkyl ethers Chemical class 0.000 claims description 4
239000005720 sucrose Substances 0.000 claims description 4
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239000004141 Sodium laurylsulphate Substances 0.000 claims 1
229940079593 drug Drugs 0.000 abstract description 34
239000003814 drug Substances 0.000 abstract description 34
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DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 4
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235000013769 triethyl citrate Nutrition 0.000 description 4
VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 4
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
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239000000600 sorbitol Substances 0.000 description 1
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
- A—HUMAN NECESSITIES
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5084—Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose

Landscapes

Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Medicinal Preparation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA2368626A 1999-03-25 2000-03-21 Cilostazol preparation Expired - Fee Related CA2368626C (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
JP11/81363		1999-03-25
JP8136399		1999-03-25
JP11/279147		1999-09-30
JP27914799		1999-09-30
PCT/JP2000/001722 WO2000057881A1 (en)	1999-03-25	2000-03-21	Cilostazol preparation

Publications (2)

Publication Number	Publication Date
CA2368626A1 CA2368626A1 (en)	2000-10-05
CA2368626C true CA2368626C (en)	2010-02-16

Family

ID=26422384

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2368626A Expired - Fee Related CA2368626C (en)	1999-03-25	2000-03-21	Cilostazol preparation

Country Status (15)

Country	Link
US (1)	US7144585B1 (es)
EP (1)	EP1162973B1 (es)
JP (1)	JP2011063611A (es)
AR (1)	AR022974A1 (es)
AT (1)	ATE296100T1 (es)
AU (1)	AU781881B2 (es)
CA (1)	CA2368626C (es)
DE (1)	DE60020343T2 (es)
EG (1)	EG23951A (es)
ES (1)	ES2238994T3 (es)
HK (1)	HK1041649B (es)
MY (1)	MY131255A (es)
PT (1)	PT1162973E (es)
TW (1)	TWI263507B (es)
WO (1)	WO2000057881A1 (es)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2006343445B8 (en) *	1998-11-02	2011-06-16	Elan Pharma International Limited	Nanoparticulate and controlled release compositions comprising a platelet aggregation inhibitor
US20030045547A1 (en)	2001-05-02	2003-03-06	Shinji Aki	Process for producing carbostyril derivatives
AU5881001A (en) *	2000-05-24	2001-12-03	Otsuka Pharma Co Ltd	Method of stabilizing preparation
GB0107106D0 (en) *	2001-03-21	2001-05-09	Boehringer Ingelheim Pharma	Powder inhaler formulations
US20050101631A1 (en) *	2002-08-01	2005-05-12	Otsuka Pharmaceuticals Company	Process for producing carbostyril derivatives
US7399864B2 (en)	2001-05-02	2008-07-15	Otsuka Pharmaceutical Co., Ltd.	Process for producing carbostyril derivatives
BR0307344A (pt)	2002-02-01	2004-12-14	Pfizer Prod Inc	Composições farmacêuticas de dispersões amorfas de fármacos e materiais formadores de microfase lipofìlica
WO2004066981A1 (en) *	2003-01-29	2004-08-12	Sun Pharmaceutical Industries Limited	Oral controlled release pharmaceutical composition containing metaxalone as active agent
BRPI0413277A (pt)	2003-08-04	2006-10-10	Pfizer Prod Inc	composições farmacêuticas de adsorvatos de medicamentos amorfos e materiais que formam microfases lipofìlicas
WO2005023225A1 (en) *	2003-09-05	2005-03-17	Ranbaxy Laboratories Limited	Cilostazol adsorbate
TWI338583B (en) *	2004-05-20	2011-03-11	Otsuka Pharma Co Ltd	Solid pharmaceutical formulation
GB0418791D0 (en) *	2004-08-23	2004-09-22	Glaxo Group Ltd	Novel process
US8506934B2 (en)	2005-04-29	2013-08-13	Robert I. Henkin	Methods for detection of biological substances
KR100667367B1 (ko) *	2005-05-10	2007-01-10	충남대학교산학협력단	용해도가 개선된 실로스타졸 복합체 조성물 및 그 제조방법
JP2008545808A (ja) *	2005-05-23	2008-12-18	エラン・ファルマ・インターナショナル・リミテッド	血小板凝集阻害薬を含むナノ粒子状および制御放出組成物
TWI383809B (zh) *	2005-06-29	2013-02-01	Otsuka Pharma Co Ltd	含有西洛他唑（ｃｉｌｏｓｔａｚｏｌ）之口腔崩解粉末
SG2014009252A (en) *	2005-12-22	2014-05-29	Otsuka Pharma Co Ltd	Method of producing drug-containing wax matrix particles, extruder to be used in the method and sustained-release preparation containing cilostazol
TW200808380A (en) *	2006-02-21	2008-02-16	Shinetsu Chemical Co	Enteric-coated preparation for site-specific delivery of drug to site within the small intestine
US8343547B2 (en) *	2006-08-08	2013-01-01	Shin-Etsu Chemical Co., Ltd.	Solid dosage form comprising solid dispersion
US8343548B2 (en)	2006-08-08	2013-01-01	Shin-Etsu Chemical Co., Ltd.	Solid dosage form comprising solid dispersion
US8519120B2 (en)	2006-08-08	2013-08-27	Shin-Etsu Chemical Co., Ltd.	Methods for producing a low-substituted hydroxypropylcellulose powder
US20080075785A1 (en) *	2006-09-22	2008-03-27	San-Laung Chow	Controlled release hydrogel formulation
US20110165236A1 (en) *	2006-09-22	2011-07-07	Biokey, Inc.	Controlled release hydrogel formulation
US8293489B2 (en)	2007-01-31	2012-10-23	Henkin Robert I	Methods for detection of biological substances
KR20080076382A (ko) *	2007-02-15	2008-08-20	(주)아모레퍼시픽	실로스타졸의 제어방출 제제 및 그 제조방법
KR20080076440A (ko) *	2007-02-16	2008-08-20	(주)아모레퍼시픽	실로스타졸의 제어방출 제제 및 그 제조방법
EP2527336A1 (en)	2007-04-25	2012-11-28	Concert Pharmaceuticals Inc.	Deuterated analogues of cilostazol
AR071706A1 (es) *	2008-05-15	2010-07-07	Otsuka Pharma Co Ltd	Una formulacion farmaceutica de cilostazol solida de liberacion sostenida y metodo de preparacion.
US8580801B2 (en)	2008-07-23	2013-11-12	Robert I. Henkin	Phosphodiesterase inhibitor treatment
WO2011037281A1 (ko)	2009-09-23	2011-03-31	한국유나이티드제약 주식회사	용출률 향상과 부작용 발현이 최소화된 실로스타졸 서방정
JP5572706B2 (ja)	2010-06-08	2014-08-13	学校法人神戸学院	コーティング粒子及びコーティング粒子の製造方法
US8968779B2 (en)	2010-06-16	2015-03-03	Teijin Pharma Limited	Controlled release coat-core tablet
KR20130106456A (ko) *	2011-04-29	2013-09-30	한국유나이티드제약 주식회사	약물 방출제어용 조성물
ES2422657B1 (es) *	2012-02-10	2014-06-11	Laboratorios Normon S.A.	Composición farmacéutica sólida de cilostazol
TWI615157B (zh)	2013-02-06	2018-02-21	大塚製藥股份有限公司	包括不定形西洛他唑的固體分散劑
EP3108245B1 (en)	2014-02-18	2020-07-22	Robert I. Henkin	Methods and compositions for diagnosing and treating loss and/or distortion of taste or smell
KR101748215B1 (ko) *	2015-05-29	2017-06-20	한국유나이티드제약 주식회사	경구용 서방성 제제
EP3409294A1 (en)	2017-06-01	2018-12-05	Przedsiebiorstwo Farmaceutyczne Lek-Am Sp Z O. O.	Tablets containing cilostazol of specific particle size distribution
JP7674080B2 (ja) *	2019-08-07	2025-05-09	沢井製薬株式会社	アビラテロン酢酸エステル含有製剤
WO2022114240A1 (en) *	2020-11-30	2022-06-02	Ssp Co., Ltd.	Solid preparation containing ibuprofen
CN114533690B (zh) *	2022-03-22	2023-03-21	许昌市中心医院	含抗凝血药物西洛他唑的新制剂及其制备方法

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4344934A (en)	1978-11-20	1982-08-17	American Home Products Corporation	Therapeutic compositions with enhanced bioavailability
DE3433239A1 (de) *	1984-09-11	1986-03-20	Bayer Ag, 5090 Leverkusen	Feste arzneizubereitung enthaltend nitrendipin und verfahren zu ihrer herstellung
EP0179583A1 (en)	1984-10-04	1986-04-30	Merck & Co. Inc.	A system for enhancing the water dissolution rate and solubility of poorly soluble drugs
US5624683A (en)	1986-08-06	1997-04-29	Eisai Co., Ltd.	Sustained-release multi-granule tablet
JPS63112519A (ja) *	1986-10-28	1988-05-17	Shin Etsu Chem Co Ltd	ニフエジピン製剤の製造方法
DE3720757A1 (de)	1987-06-24	1989-01-05	Bayer Ag	Dhp-manteltablette
FR2627696B1 (fr)	1988-02-26	1991-09-13	Fournier Innovation Synergie	Nouvelle forme galenique du fenofibrate
JP2764274B2 (ja) *	1988-03-28	1998-06-11	株式会社ミドリ十字	医薬組成物
JP2871776B2 (ja) *	1989-03-28	1999-03-17	カロライナメディカルプロダクツインコーポレイテッド	スピロノラクトン組成物
JP2642486B2 (ja) *	1989-08-04	1997-08-20	田辺製薬株式会社	難溶性薬物の超微粒子化法
US5145684A (en)	1991-01-25	1992-09-08	Sterling Drug Inc.	Surface modified drug nanoparticles
FI93924C (fi)	1991-09-17	1995-06-26	Martti Lauri Antero Marvola	Menetelmä säädellysti lääkeainetta vapauttavan valmisteen valmistamiseksi
WO1993005770A1 (fr)	1991-09-20	1993-04-01	Fujisawa Pharmaceutical Co., Ltd.	Preparation a longue duree d'action
DK0661045T3 (da)	1992-09-18	2002-10-28	Yamanouchi Pharma Co Ltd	Hydrogelpræparat med forsinket frigivelse
JP3681185B2 (ja) *	1994-03-31	2005-08-10	太田製薬株式会社	錠剤製造用ニフェジピン固体粒子組成物
JPH07291869A (ja) *	1994-04-26	1995-11-07	Otsuka Pharmaceut Factory Inc	経口投与用製剤
CN1128497A (zh) *	1994-05-17	1996-08-07	株式会社大塚制药工场	在血液的体外循环中防止血液凝固的方法及所应用的抗血栓性药物释放装置
JPH0873354A (ja) *	1994-09-07	1996-03-19	Otsuka Pharmaceut Co Ltd	気道過敏症および／または気道障害の予防、治療剤
US6117455A (en) *	1994-09-30	2000-09-12	Takeda Chemical Industries, Ltd.	Sustained-release microcapsule of amorphous water-soluble pharmaceutical active agent
JP3799093B2 (ja) *	1995-01-10	2006-07-19	大塚製薬株式会社	樹脂粒状物およびこれを含有する医療製剤
WO1996021448A1 (en) *	1995-01-10	1996-07-18	Otsuka Pharmaceutical Co., Ltd.	Resin particle, medical material and pharmaceutical preparation containing said resin particle
JP4484247B2 (ja) *	1995-02-24	2010-06-16	エランファーマインターナショナル，リミティド	ナノ粒子分散体を含有するエアロゾル
AUPN651895A0 (en) *	1995-11-10	1995-12-07	Down Hole Technologies Pty Ltd	Spear head assembly
JPH1067657A (ja)	1996-06-18	1998-03-10	Otsuka Pharmaceut Co Ltd	マルチプルユニット型持続性製剤
AU2976897A (en) *	1996-06-18	1998-01-07	Otsuka Pharmaceutical Co., Ltd.	Multiple-unit type prolonged action drug preparation
JPH1077234A (ja) *	1996-09-05	1998-03-24	Ohara Yakuhin Kogyo Kk	経口用固形製剤及びその製造方法
FR2758461A1 (fr)	1997-01-17	1998-07-24	Pharma Pass	Composition pharmaceutique presentant une biodisponibilite elevee et son procede de preparation
FR2758459B1 (fr) *	1997-01-17	1999-05-07	Pharma Pass	Composition pharmaceutique de fenofibrate presentant une biodisponibilite elevee et son procede de preparation
US6294192B1 (en) *	1999-02-26	2001-09-25	Lipocine, Inc.	Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents
JP4748839B2 (ja) *	1999-03-25	2011-08-17	大塚製薬株式会社	シロスタゾール製剤
US6825214B2 (en) *	2000-08-14	2004-11-30	Teva Pharmaceutical Industries, Ltd.	Substantially pure cilostazol and processes for making same
US20050255155A1 (en) *	2004-05-11	2005-11-17	Glenmark Pharmaceuticals Limited	Modified release cilostazol compositions

2000
- 2000-03-11 EG EG20000310A patent/EG23951A/xx active
- 2000-03-17 AR ARP000101208A patent/AR022974A1/es unknown
- 2000-03-20 MY MYPI20001097A patent/MY131255A/en unknown
- 2000-03-21 HK HK02103425.7A patent/HK1041649B/en active IP Right Revival
- 2000-03-21 US US09/555,026 patent/US7144585B1/en not_active Expired - Fee Related
- 2000-03-21 CA CA2368626A patent/CA2368626C/en not_active Expired - Fee Related
- 2000-03-21 EP EP00909776A patent/EP1162973B1/en not_active Expired - Lifetime
- 2000-03-21 PT PT00909776T patent/PT1162973E/pt unknown
- 2000-03-21 ES ES00909776T patent/ES2238994T3/es not_active Expired - Lifetime
- 2000-03-21 AU AU31965/00A patent/AU781881B2/en not_active Ceased
- 2000-03-21 AT AT00909776T patent/ATE296100T1/de active
- 2000-03-21 DE DE60020343T patent/DE60020343T2/de not_active Expired - Lifetime
- 2000-03-21 WO PCT/JP2000/001722 patent/WO2000057881A1/en not_active Ceased
- 2000-03-24 TW TW089105430A patent/TWI263507B/zh not_active IP Right Cessation
2010
- 2010-11-19 JP JP2010258873A patent/JP2011063611A/ja active Pending

Also Published As

Publication number	Publication date
US7144585B1 (en)	2006-12-05
JP2011063611A (ja)	2011-03-31
HK1041649B (en)	2005-11-04
ES2238994T3 (es)	2005-09-16
EG23951A (en)	2008-01-29
AU3196500A (en)	2000-10-16
PT1162973E (pt)	2005-08-31
MY131255A (en)	2007-07-31
AR022974A1 (es)	2002-09-04
AU781881B2 (en)	2005-06-16
TWI263507B (en)	2006-10-11
DE60020343T2 (de)	2006-01-26
DE60020343D1 (de)	2005-06-30
HK1041649A1 (en)	2002-07-19
EP1162973B1 (en)	2005-05-25
WO2000057881A1 (en)	2000-10-05
ATE296100T1 (de)	2005-06-15
CA2368626A1 (en)	2000-10-05
EP1162973A1 (en)	2001-12-19

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JPH03145418A (ja)	1991-06-20	塩基性薬物塩酸塩の徐放性製剤
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